crossing96/oncoscreening huggingface dataset:
Long-term renal function following radical cystectomy and ileal conduit creation.	BACKGROUND: Treatment for bladder cancer includes radical cystectomy (RC) and urinary diversion; RC is associated with long-term morbidity, kidney impairment and mortality. AIM: To identify risk factors associated with postoperative long-term kidney function and mortality. METHODS: Retrospective study of patients with RC and urinary diversion in Beaumont Hospital from 1996 to 2016. We included patients who had follow-up at least 2 years post-procedure. We assessed estimated glomerular filtration rate (eGFR) preoperatively and yearly post-procedure, dialysis commencement and mortality. Cox and Fine-Gray regression analyses were applied; p-value < 0.05 was considered significant. RESULTS: We included 264 patients, median age 68.3 years, 73.7% males. The most common diagnosis was bladder cancer 93.3%, TNM stages T ≥ 2 75.9%, N ≥ 1 47.6% and M1 28%. The median eGFR preoperative was 65.8 ml/min/1.73m(2) and after 2 years 58.2 ml/min/1.73m(2) (p: 0.009); 5.3% required chronic dialysis and 32.8% had a decrease > 10 ml/min/1.73m(2). Risk factors associated with ESKD and start dialysis included younger age (HR: 0.90, CI 95% 0.87-0.94) and lower pre-operative eGFR (HR: 0.97, CI 95% 0.94-1.00). Overall mortality was 43.2% and 54.1% at 5 and 10 years, respectively; risk factors were older age (HR: 1.04, CI 95% 1.02-1.06), tumour stage T ≥ 2 (HR: 2.22, CI 95% 1.39-3.54) and no chemotherapy (HR: 1.72, CI 95% 1.18-2.51). Limitations include retrospective design, absence of control group and single centre experience. CONCLUSIONS: Patients with RC are at risk of progressive kidney function deterioration and elevated mortality and the main risk factors associated were age and preoperative eGFR. Regular monitoring of kidney function will permit early diagnosis and treatment.	bladder
DUSP2 affects bladder cancer prognosis by down-regulating MEK/ERK and P38 MAPK signaling pathways through PTPN7.	BACKGROUND: As one of the leading causes of cancer death worldwide, bladder cancer (BCa) ranks 12th in incidence rate. Dual Specific Phosphatase 2 (DUSP2) is a member of the bispecific protein phosphatase subfamily. DUSP2 is closely related to the prognosis of cancer, but the role of DUSP2 in bladder cancer is still unclear. This study aims to explore how DUSP2 affects the prognosis of bladder cancer and clarify the important mechanism in bladder cancer. METHODS: Bioinformatics and experiments have detected the anti-tumor effect of DUSP2. Construct a DUSP2 overexpression cell model, and then use protein blotting experiments to verify the efficiency of transfection. The effects of DUSP2 on proliferation, metastasis, apoptosis, epithelial mesenchymal transition (EMT) and immune invasion of bladder cancer cells were detected in vitro or in vivo. In addition, the mechanism of DUSP2 regulating MEK/ERK through PTPN7 pathway and P38 MAPK inhibiting the progression of bladder cancer was also discussed. RESULTS: The expression of DUSP2 was down regulated in bladder cancer samples and cell lines. The overexpression of DUSP2 inhibits the proliferation, metastasis and immune microenvironment of bladder cancer cells. In addition, we confirmed that DUSP2 regulates MEK/ERK and P38 MAPK through PTPN7 pathway to inhibit the progression of bladder cancer. CONCLUSION: DUSP2 inhibits the progression of bladder cancer by regulating PTPN7. These results suggest that DUSP2/PTPN7/MEK/ERK pathway may become a new therapeutic target for bladder cancer.	bladder
Association of metabolic syndrome and its components with the risk of urologic cancers: a prospective cohort study.	OBJECTIVE: To investigate the association between metabolic syndrome (MetS) and its components and the risk of developing urologic cancers. METHODS: This study included 101,510 observation subjects from May 2006 to December 2007. The subjects received questionnaires and were subjected to clinical and laboratory examinations to collect data on baseline population characteristics, waist circumference (WC), blood pressure (BP), blood glucose, blood lipids, lifestyle, and past disease history. Finally, follow-up was conducted from the date of recruitment to December 31, 2019. Cox proportional hazards modelling was applied to analyze the association between MetS and its components and the risk of developing urologic cancers. RESULTS: A total of 97,975 observation subjects met the inclusion criteria. The cumulative follow-up period included 1,209,178.65 person-years, and the median follow-up time was 13.03 years. During the follow-up period, 485 cases of urologic cancers (165 cases of kidney cancer, 134 cases of prostate cancer, 158 cases of bladder cancer, and 28 cases of other urologic cancers) were diagnosed. The log-rank test results for the cumulative incidences of urologic cancer, kidney cancer, and prostate cancer indicated significant (P < 0.01) differences between the MetS and non-MetS groups (0.70% vs. 0.48%, 0.27% vs. 0.15%, and 0.22% vs. 0.13%, respectively). Compared to the non-MetS group, the risk of developing urologic [HR (95% CI) = 1.29 (1.08-1.55)], kidney [HR (95% CI) = 1.74 (1.28-2.37)], and prostate [HR (95% CI) = 1.47 (1.04-2.07)] cancers was significantly higher in the MetS group. In the MetS group, elevated BP increased the risk of developing of urologic cancer [HRs (95% CI) = 1.35 (1.10-1.66)] and kidney cancer [HR (95% CI) = 1.74 (1.21-2.51)], while central obesity increased the risk of developing prostate cancer [HR (95% CI) = 1.68 (1.18-2.40)]. CONCLUSIONS: MetS increased the risk of developing urologic, kidney, and prostate cancers but had no association with the development of bladder cancer.	bladder
Secondary tumours in orthotopic neobladder using isolated gut segment post radical cystectomy for urothelial carcinoma: a systematic review.	BACKGROUND: Urothelial carcinoma recurrence of an orthotopic neobladder created from bowel segment is a rare occurrence. The usage of bowel segments to create neobladder following cystectomy for urinary diversion is growing yet there still remains a large gap in the literature about recurrence in neobladder. We carry out the first systematic review to outline current details of urothelial cancer recurrences in a neobladder, diagnostic approach, management and long term prognosis. METHOD: We carried out a systematic review searching databases PubMed (MEDLINE), Scopus and Web of Science. Only studies reporting on urothelial carcinoma recurrence of the neobladder with or without multi-focal disease were reported. A quality assessment tool was utilized to ensure all studies met quality standards. RESULTS: Fifteen studies were included in the systematic review meeting inclusion criteria. Fourteen of these studies were cases in men where pT3 disease was the most prevalent (29%). The most common symptomology was macroscopic haematuria seen in eight patients (53.33%). Management varied among cases and including adjuvant chemotherapy regimens and surgical interventions consisting of endoscopic resection to robotic neocystectomy and nephroureterectomy. Follow up period for these patients was up to 38 months and 55% of patients did not see a recurrence. CONCLUSION: The nature of recurrence is hypothesised to be due to seeding of urothelial cells into the non-urothelial surfaces compatible for both implantation and growth. We present the first systematic review to report on recurrence rates and details of diagnosis and outcomes of various management regimes for urothelial carcinoma of the neobladder.	bladder
Evaluating interactions of polygenic risk scores and NAT2 genotypes with tobacco smoking in bladder cancer risk.	Tobacco smoking is the most important risk factor for bladder cancer. Previous studies have identified the N-acetyltransferase (NAT2) gene in association with bladder cancer risk. The NAT2 gene encodes an enzyme that metabolizes aromatic amines, carcinogens commonly found in tobacco smoke. In our study, we evaluated potential interactions of tobacco smoking with NAT2 genotypes and polygenic risk score (PRS) for bladder cancer, using data from the UK Biobank, a large prospective cohort study. We used Cox proportional hazards models to measure the strength of the association. The PRS was derived using genetic risk variants identified by genome-wide association studies for bladder cancer. With an average of 10.1 years of follow-up of 390 678 eligible participants of European descent, 769 incident bladder cancer cases were identified. Current smokers with a PRS in the highest tertile had a higher risk of developing bladder cancer (HR: 6.45, 95% CI: 4.51-9.24) than current smokers with a PRS in the lowest tertile (HR: 2.41, 95% CI: 1.52-3.84; P for additive interaction = <.001). A similar interaction was found for genetically predicted metabolizing NAT2 phenotype and tobacco smoking where current smokers with the slow NAT2 phenotype had an increased risk of developing bladder cancer (HR: 5.70, 95% CI: 2.64-12.30) than current smokers with the fast NAT2 phenotype (HR: 3.61, 95% CI: 1.14-11.37; P for additive interaction = .100). Our study provides support for considering both genetic and lifestyle risk factors in developing prevention measures for bladder cancer.	bladder
Chronic Obstructive Pulmonary Disease Mortality in Bladder Cancer Patients: A SEER-Based Competing Risk Analysis.	PURPOSE: This study was designed to evaluate risk of mortality from chronic obstructive pulmonary disease (COPD) in patients with bladder cancer (BC). METHODS AND MATERIALS: Data on patients diagnosed with BC by pathology between 2000 and 2016 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Based on reference data from the general population, the standardized mortality rate (SMR) is calculated. Nelson-Aalen cumulative hazard curves were used for assessment of the risk of COPD mortality in BC patients. Multivariable competing risk models were conducted. The proportional hazards assumption was tested using Schoenfeld residuals, which were scaled and plotted over time for each risk factor. RESULTS: A total of 237,563 BC patients were identified for further analysis from the SEER database, 5,198 of these patients experienced COPD mortality; the overall SMR for COPD mortality in BC patients was 1.58 (95% CI: 1.54-1.63). Age, race, year of diagnosis, histologic type, summary stage, surgery, marital status, college education level, and median household income independently predicted COPD mortality in BC patients. CONCLUSIONS: In comparison to the general population, the risk of COPD mortality is significantly higher in patients with BC. Pre-identification of high-risk groups and respiratory care provisions are important measures to effectively improve survival in this group of patients.	bladder
Gene of the month: GATA3.	GATA binding protein 3 (GATA3) is a zinc-finger pioneer transcription factor involved in diverse processes. GATA3 regulates gene expression through binding nucleosomal DNA and facilitating chromatin remodelling. Post-translational modifications modulate its activity. During development, GATA3 plays a key role in cell differentiation. Mutations in GATA3 are linked to breast and bladder cancer. GATA3 expression is a feature of the luminal subtype of bladder cancer and has implications for immune status and therapeutic response. It also has clinical relevance in squamous cell carcinomas and soft tissue sarcomas. This paper reviews the structure and function of GATA3, its role in cancer and its use and pitfalls as an immunohistochemical marker.	bladder
Consultation on UTUC II Stockholm 2022: diagnostic and prognostic methods-what's around the corner?	PURPOSE: To map current literature and provide an overview of upcoming future diagnostic and prognostic methods for upper tract urothelial carcinoma (UTUC), including translational medical science. METHODS: A scoping review approach was applied to search the literature. Based on the published literature, and the experts own experience and opinions consensus was reached through discussions at the meeting Consultation on UTUC II in Stockholm, September 2022. RESULTS: The gene mutational profile of UTUC correlates with stage, grade, prognosis, and response to different therapeutic strategies. Analysis of pathway proteins downstream of known pathogenic mutations might be an alternative approach. Liquid biopsies of cell-free DNA may detect UTUC with a higher sensitivity and specificity than urinary cytology. Extracellular vesicles from tumour cells can be detected in urine and may be used to identify the location of the urothelial carcinoma in the urinary tract. 3D microscopy of UTUC samples may add information in the analysis of tumour stage. Chemokines and chemokine receptors were linked to overall survival and responsiveness to neoadjuvant chemotherapy in muscle-invasive bladder cancer, which is potentially also of interest in UTUC. CONCLUSION: Current diagnostic methods for UTUC have shortcomings, especially concerning prognostication, which is important for personalized treatment decisions. There are several upcoming methods that may be of interest for UTUC. Most have been studied for urothelial carcinoma of the bladder, and it is important to keep in mind that UTUC is a different entity and not all methods are adaptable or applicable to UTUC.	bladder
CT-based deep learning radiomics nomogram for the prediction of pathological grade in bladder cancer: a multicenter study.	BACKGROUND: To construct and assess a computed tomography (CT)-based deep learning radiomics nomogram (DLRN) for predicting the pathological grade of bladder cancer (BCa) preoperatively. METHODS: We retrospectively enrolled 688 patients with BCa (469 in the training cohort, 219 in the external test cohort) who underwent surgical resection. We extracted handcrafted radiomics (HCR) features and deep learning (DL) features from three-phase CT images (including corticomedullary-phase [C-phase], nephrographic-phase [N-phase] and excretory-phase [E-phase]). We constructed predictive models using 11 machine learning classifiers, and we developed a DLRN by combining the radiomic signature with clinical factors. We assessed performance and clinical utility of the models with reference to the area under the curve (AUC), calibration curve, and decision curve analysis (DCA). RESULTS: The support vector machine (SVM) classifier model based on HCR and DL combined features was the best radiomic signature, with AUC values of 0.953 and 0.943 in the training cohort and the external test cohort, respectively. The AUC values of the clinical model in the training cohort and the external test cohort were 0.752 and 0.745, respectively. DLRN performed well on both data cohorts (training cohort: AUC = 0.961; external test cohort: AUC = 0.947), and outperformed the clinical model and the optimal radiomic signature. CONCLUSION: The proposed CT-based DLRN showed good diagnostic capability in distinguishing between high and low grade BCa.	bladder
Xpert bladder cancer monitor to predict the need for a second TURB (MoniTURB trial).	To determine whether Xpert bladder cancer monitor, a noninvasive PCR-based biomarker test, can predict the need for 2nd transurethral resection of the bladder (TURB) better than clinical assessment. Patients scheduled for TURB were prospectively screened. After initial TURB, patients were assigned to 2nd TURB or follow-up cystoscopy at 3 months (FU) by clinicians' discretion. Central urine cytology and Xpert monitor tests were performed prior to the 1st TURB and 2nd TURB or FU, respectively. Statistical analysis to compare clinical assessment and Xpert monitor comprised sensitivity (SENS), specificity (SPEC), NPV and PPV. Of 756 screened patients, 171 were included (114 with 2nd TURB, 57 with FU). Residual tumors were detected in 34 patients who underwent 2nd TURB, and recurrent tumors were detected in 2 patients with FU. SENS and SPEC of Xpert monitor were 83.3% and 53.0%, respectively, PPV was 32.6% and NPV was 92.1%. Clinical risk assessment outperformed Xpert monitor. In patients with pTa disease at initial TURB, Xpert monitor revealed a NPV of 96%. Xpert monitor was not superior than clinical assessment in predicting the need for 2nd TURB. It might be an option to omit 2nd TURB for selected patients with pTa disease.	bladder
The prognostic significance of histologic variant on survival outcomes in patients with metastatic urothelial carcinoma receiving immune checkpoint inhibitor therapy.	BACKGROUND: While the treatment guidelines have been established for pure urothelial carcinoma (pUC), patients with variant type urothelial carcinoma (vUC) face limited effective treatment options. The effectiveness of immune checkpoint inhibitors (ICI) in patients with vUC remains uncertain and necessitates additional research. METHOD: We conducted a retrospective, multicenter study to explore the effectiveness of ICI in patients with pUC or vUC in Taiwan. We evaluated the overall response rate (ORR) through univariate logistic regression analysis and examined the overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier analysis. Additionally, we employed univariate and multivariate Cox proportional hazards models to analyze the data. RESULT: A total of 142 patients (116 pUC, 26 vUC) were included in our final analysis. The ORR was marginally higher in patients with pUC compared to those with vUC (34.5% vs. 23.1%, p = 0.26). Among all patients, 12.9% with pUC achieved a complete response (CR) after ICI treatment, while no vUC cases achieved CR (p = 0.05). There were no significant differences in PFS (median 3.6 months vs. 4.1 months, p = 0.34) or OS (median 16.3 months vs. 11.0 months, p = 0.24) when comparing patients with pUC or vUC. In the subgroup analysis, patients with pUC who underwent first-line ICI treatment exhibited significantly improved OS compared to those with vUC (24.6 months vs. 9.1 months, p = 0.004). CONCLUSION: The use of ICI as monotherapy is a feasible and effective treatment approach for patients with metastatic vUC.	bladder
The impact of mutational clonality in predicting the response to immune checkpoint inhibitors in advanced urothelial cancer.	Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment and can result in complete remissions even at advanced stages of the disease. However, only a small fraction of patients respond to the treatment. To better understand which factors drive clinical benefit, we have generated whole exome and RNA sequencing data from 27 advanced urothelial carcinoma patients treated with anti-PD-(L)1 monoclonal antibodies. We assessed the influence on the response of non-synonymous mutations (tumor mutational burden or TMB), clonal and subclonal mutations, neoantigen load and various gene expression markers. We found that although TMB is significantly associated with response, this effect can be mostly explained by clonal mutations, present in all cancer cells. This trend was validated in an additional cohort. Additionally, we found that responders with few clonal mutations had abnormally high levels of T and B cell immune markers, suggesting that a high immune cell infiltration signature could be a better predictive biomarker for this subset of patients. Our results support the idea that highly clonal cancers are more likely to respond to ICI and suggest that non-additive effects of different signatures should be considered for predictive models.	bladder
Insights into vitamin A in bladder cancer, lack of attention to gut microbiota?	Vitamin A has long been associated with bladder cancer, and many exogenous vitamin A supplements, vitamin A derivatives, and synthetic drugs have been investigated over the years. However, the effectiveness of these strategies in clinical practice has not met expectations, and they have not been widely adopted. Recent medical research on intestinal flora has revealed that bladder cancer patients exhibit reduced serum vitamin A levels and an imbalance of gut microbiota. In light of the close relationship between gut microbiota and vitamin A, one can speculate that a complex regulatory mechanism exists between the two in the development and occurrence of bladder cancer. As such, further exploration of their interaction in bladder cancer may help guide the use of vitamin A for preventive purposes. During the course of this review, attention is paid to the influence of intestinal microbiota on the vitamin A metabolism and the RA signaling pathway, as well as the mutual promotion relationships between them in the prevention of bladder cancer, In addition, it emphasizes the importance of intestinal microbiota for bladder cancer prevention and treatment.	bladder
Anticancer effects of cell-free culture supernatant of Escherichia coli in bladder cancer cell line: New insight into the regulation of inflammation.	Bladder cancer (BC) is the 10th most common malignancy in worldwide, with substantial mortality and morbidity if not treated effectively. According to various research, inflammatory circumstances majorly impact the microenvironment of bladder cancer, and the chronic presence of cytokines and chemokines promotes tumor progression. In this investigation, we explored the impact of cell-free culture supernatant ofEscherichia colistrain 536 on inflammatory cytokines and chemokines in bladder cancer model microarray data (GSE162251). Then we examined in silico outcomes on human bladder cancer cell line 5637 to verify and extrapolate findings. This investigation revealed for the first time that this compound has potent suppressor effects on interleukin 1 beta (IL-1β), C-C motif chemokine ligand 2 (CCL2), and C-X3-C motif chemokine ligand 1 (CX3CL1) gene expression as well as increased NAD(P)H quinone dehydrogenase 1 (NQO1), as an anti-oxidant agent, gene expression in 4, 8, and 24 h. Moreover, we confirmed that c-MYC, a member of the MYC proto-oncogene family, gene expression reduced in 5637 cells in 4 h and then followed up its expression in 8 and 24 h. In addition, our investigation demonstrated that the supernatant raised the BCL2-Associated X Protein/B-cell lymphoma 2 (BAX/BCL2) ratio, and subsequent flow cytometry analysis demonstrated that the supernatant induction apoptosis and necrosis. In conclusion, our findings demonstrate that this compound is a potential candidate for the suppression of bladder cancer progression.	bladder
LncRNA BCCE4 Genetically Enhances the PD-L1/PD-1 Interaction in Smoking-Related Bladder Cancer by Modulating miR-328-3p-USP18 Signaling.	Identification of cancer-associated variants, especially those in functional regions of long noncoding RNAs (lncRNAs), has become an essential task in tumor etiology. However, the genetic function of lncRNA variants involved in bladder cancer susceptibility remains poorly understood. Herein, it is identified that the rs62483508 G > A variant in microRNA response elements (MREs) of lncRNA Bladder cancer Cell Cytoplasm-Enriched abundant transcript 4 (BCCE4) is significantly associated with decreased bladder cancer risk (odds ratio = 0.84, P = 7.33 × 10(-8) ) in the Chinese population (3603 cases and 4986 controls) but not in the European population. The protective genetic effect of the rs62483508 A allele is found in smokers or cigarette smoke-related carcinogen 4-aminobiphenyl (4-ABP) exposure. Subsequent biological experiments reveal that the A allele of rs62483508 disrupts the binding affinity of miR-328-3p to facilitate USP18 from miRNA-mediated degradation and thus specifically attenuates the downstream PD-L1/PD-1 interaction. LncRNA BCCE4 is also enriched in exosomes from bladder cancer plasma, tissues, and cells. This comprehensive study clarifies the genetic mechanism of lncRNA BCCE4 in bladder cancer susceptibility and its role in the regulation of the immune response in tumorigenesis. The findings provide a valuable predictor of bladder cancer risk that can facilitate diagnosis and prevention.	bladder